Severn Sound, located in Lake Huron, is one of nine (out of 43) Areas of Concern (AOC) that have been delisted. In 1987, Severn Sound was designated an AOC due to eutrophication and habitat loss, and after mitigation measures, was delisted in 2003. Information used to delist Severn Sound was based in part on a long-term water quality program by the Ministry of the Environment and Severn Sound Environmental Association that has been uninterrupted since 1973. Such temporally extensive water quality programs are rare in the Great Lakes, especially those that capture decadal periods of environmental change driven by government regulations, species invasions, and climate change. To improve our understanding of long-term water quality in Severn Sound, we applied a suite of statistical methods to assess trends and patterns of change across four embayments from 1973 to 2020 for the following water quality variables: chlorophyll a, ammonia + ammonium, nitrate + nitrite, total organic nitrogen, total nitrogen, total phosphorus, Secchi disk visibility, and water temperature. We found that the embayments in Severn Sound have significant differences across stations in water quality parameters such as total phosphorus, total nitrogen, Secchi disk visibility, and water temperature. Overall decreases in total phosphorus and chlorophyll a and increases in Secchi disk visibility illustrate the influences of nutrient reduction strategies and potential influences from invasive dreissenid mussels. Although an important driver of water quality changes, surface water temperature change was variable during the study, likely due to site-specific differences and inherent data variability over time.